Genetic control of the autoimmune response of mice to homologous thyroglobulin will be assessed in terms of antibody production and lymphocytic thyroiditis. Three genetic loci have been implicated: (1) K or I region control; (2) intra-H-2 control outside of the K or I region; and (3) extra H-2 control. Efforts will be made to define each locus by the use of appropriate recombinants, to determine the cellular basis of gene expression and to distinguish helper (effector) from suppressor activities of cells and cell products. The role of various classes of adjuvants, including Freund's, lipopolysaccharide and polynucleotides in abrogating self-tolerance will be compared.